Ontology Enrichment from Free-text Clinical Documents: A Comparison of Alternative Approaches

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships, as well as difficulty in updating the ontology as domain knowledge changes. Methodologies developed in the fields of Natural Language Processing (NLP), Information Extraction (IE), Information Retrieval (IR), and Machine Learning (ML) provide techniques for automating the enrichment of ontology from free-text documents. In this dissertation, I extended these methodologies into biomedical ontology development. First, I reviewed existing methodologies and systems developed in the fields of NLP, IR, and IE, and discussed how existing methods can benefit the development of biomedical ontologies. This previously unconducted review was published in the Journal of Biomedical Informatics. Second, I compared the effectiveness of three methods from two different approaches, the symbolic (the Hearst method) and the statistical (the Church and Lin methods), using clinical free-text documents. Third, I developed a methodological framework for Ontology Learning (OL) evaluation and comparison. This framework permits evaluation of the two types of OL approaches that include three OL methods. The significance of this work is as follows: 1) The results from the comparative study showed the potential of these methods for biomedical ontology enrichment. For the two targeted domains (NCIT and RadLex), the Hearst method revealed an average of 21% and 11% new concept acceptance rates, respectively. The Lin method produced a 74% acceptance rate for NCIT; the Church method, 53%. As a result of this study (published in the Journal of Methods of Information in Medicine), many suggested candidates have been incorporated into the NCIT; 2) The evaluation framework is flexible and general enough that it can analyze the performance of ontology enrichment methods for many domains, thus expediting the process of automation and minimizing the likelihood that key concepts and relationships would be missed as domain knowledge evolves

Game-theoretical approach for task allocation problems with constraints

The distributed task allocation problem, as one of the most interesting distributed optimization challenges, has received considerable research attention recently. Previous works mainly focused on the task allocation problem in a population of individuals, where there are no constraints for affording task amounts. The latter condition, however, cannot always be hold. In this paper, we study the task allocation problem with constraints of task allocation in a game-theoretical framework. We assume that each individual can afford different amounts of task and the cost function is convex. To investigate the problem in the framework of population games, we construct a potential game and calculate the fitness function for each individual. We prove that when the Nash equilibrium point in the potential game is in the feasible solutions for the limited task allocation problem, the Nash equilibrium point is the unique globally optimal solution. Otherwise, we also derive analytically the unique globally optimal solution. In addition, in order to confirm our theoretical results, we consider the exponential and quadratic forms of cost function for each agent. Two algorithms with the mentioned representative cost functions are proposed to numerically seek the optimal solution to the limited task problems. We further perform Monte Carlo simulations which provide agreeing results with our analytical calculations

pH-responsive Pickering emulsions stabilized by silica nanoparticles in combination with a conventional zwitterionic surfactant

pH-responsive oil-in-water Pickering emulsions were prepared simply by using negatively charged silica nanoparticles in combination with a trace amount of a zwitterionic carboxyl betaine surfactant as stabilizer. Emulsions are stable to coalescence at pH 5 but phase separate completely at pH > 8.5. In acidic solution, the carboxyl betaine molecules become cationic allowing them to adsorb on silica nanoparticles via electrostatic interactions, thus hydrophobizing and flocculating them enhancing their surface activity. Upon increasing the pH, surfactant molecules are converted to witterionic form and significantly desorb from particles surfaces triggering de-hydrophobization and coalescence of oil droplets within the emulsion. The pH-responsive emulsion can be cycled between stable and unstable many times upon alternating the pH of the aqueous phase. The average droplet size in re-stabilized emulsions at low pH however increases gradually after four cycles due to the accumulation of NaCl. Experimental evidence including adsorption isotherms, zeta potentials, microscopy and three-phase contact angles is given to support the postulated mechanisms

The Assessment on Synergistic Activity of Ebselen and Silver Ion Against Yersinia pseudotuberculosis

Yersinia pseudotuberculosis is a foodborne zoonotic bacterium that is pathogenic to guinea pigs, rabbits, and mice. It also causes pseudotuberculosis in humans. However, it still lacked the scientific basis for control. Here, we found out that Ebselen (EbSe) exhibited synergistic antibacterial activity with silver nitrate (Ag+) against Y. pseudotuberculosis YpIII strain with high efficacy in vitro using UV-visible light absorption spectrum, 5,5’-dithiobis-(2-nitrobenzoic acid), laser scanning confocal microscope, flow cytometry, transmission electron microscopy and Western blotting assays. The depletion of total glutathione (GSH) amount and inhibition of thioredoxin reductase (TrxR) activity in thiol-dependent redox system revealed the destructiveness of EbSe-Ag+-caused intracellular oxidative stress. Furthermore, a YpIII-caused mice gastroenteritis model was constructed. EbSe-Ag+ significantly reduced bacterial loads with low toxicity. It also down-regulated the expression levels of interferon (IL)-1β and tumor necrosis factor-α, up-regulated the expression level of IL-10 on-site. All the in vivo results demonstrated the antibacterial activity and immune-modulatory property of EbSe-Ag+. Collectively, these results provided academic fundament for further analysis and development of EbSe-Ag+ as the antibacterial agents for pseudotuberculosis control

Using publicly available data, a physiologically-based pharmacokinetic model and Bayesian simulation to improve arsenic non-cancer dose-response

Publicly available data can potentially examine the relationship between environmental exposure and public health, however, it has not yet been widely applied. Arsenic is of environmental concern, and previous studies mathematically parameterized exposure duration to create a link between duration of exposure and increase in risk. However, since the dose metric emerging from exposure duration is not a linear or explicit variable, it is difficult to address the effects of exposure duration simply by using mathematical functions. To relate cumulative dose metric to public health requires a lifetime physiologically-based pharmacokinetic (PBPK) model, yet this model is not available at a population level. In this study, the data from the U.S. total diet study (TDS, 2006–2011) was employed to assess exposure: daily dietary intakes for total arsenic (tAs) and inorganic arsenic (iAs) were estimated to be 0.15 and 0.028 μg/kg/day, respectively. Meanwhile, using National Health and Nutrition Examination Survey (NHANES, 2011–2012) data, the fraction of urinary As(III) levels (geometric mean: 0.31 μg/L) in tAs (geometric mean: 7.75 μg/L) was firstly reported to be approximately 4%. Together with Bayesian technique, the assessed exposure and urinary As(III) concentration were input to successfully optimize a lifetime population PBPK model. Finally, this optimized PBPK model was used to derive an oral reference dose (Rfd) of 0.8 μg/kg/day for iAs exposure. Our study also suggests the previous approach (by using mathematical functions to account for exposure duration) may result in a conservative Rfd estimation

Thermoresponsive Pickering emulsions stabilized by silica nanoparticles in combination with alkyl polyoxyethylene ether nonionic surfactant

We put forward a simple protocol to prepare thermo-responsive Pickering emulsions. Using hydrophilic silica nanoparticles in combination with a low concentration of alkyl polyoxyethylene monododecyl ether (C12En) nonionic surfactant as emulsifier, oil-in-water (o/w) emulsions can be obtained which are stable at room temperature but demulsified at elevated temperature. The stabilization can be restored once the separated mixture is cooled and re-homogenized, and this stabilization-destabilization behavior can be cycled many times. It is found that the adsorption of nonionic surfactant at the silica nanoparticle-water interface via hydrogen bonding between the oxygen atoms in the polyoxyethylene headgroup and the SiOH groups on particle surfaces at low temperature is responsible for the in situ hydrophobization of the particles rendering them surface-active. De-hydrophobization can be achieved at elevated temperature due to weakening or loss of this hydrogen bonding. The time required for demulsification decreases with increasing temperature and the temperature interval between stabilization and destabilization of the emulsions is affected by the surfactant headgroup length. Experimental evidence including microscopy, adsorption isotherms and three-phase contact angles is provided to support the mechanism

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices